CIHM 
Microfiche 
Series 
(Monographs) 


ICIVIH 

Collection  H9 
microfiches 
(monographies) 


Canadian  Institute  for  Historical  Microroproductions  /  Instltut  canadien  de  microreproductions  historiques 


(6^1099 


Technical  a; . .  3ibliographic  Notes  /  Notes  techniques  et  bibliographiques 


t  '.o  cO'ain  the  best  original 
roat-'es  of  this  copy  which 


Thfc  ..istiiute  has  atte'^s" 

copy  available  for  film."! 

may  be  bibliographically  unuiue,  uhioh  may  alter  any  of 

the   images   in   the   reproduciirMi,    or  which    may 

significantly  change  the  usual  method  of  filming  are 

checked  below. 


□ 


D 


n 


n 


Coloured  covers  / 
Cnuverture  de  couleur 


□    Covers  damaged  / 
Couverture  endommagee 

□    Covers  restored  and/or  lamiinated  / 
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nOnly  edition  available  / 
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D 


Tight  binding  may  cause  shadows  or  distortion  along 
interior  margin  /  La  reliure  serree  peut  causer  de 
i'ombre  ou  de  la  distorsion  le  long  de  la  marge 
interieure. 

Blank  leaves  aaded  during  restorations  may  appear 
within  the  text.  Whenever  possible,  these  have  been 
omitted  from  filming  /  II  se  peut  que  certaines  pages 
blanches  a|outees  lors  d'une  restauration 
apparaissent  dans  le  texte.  mais,  lorsque  cela  r-tait 
possible,  ces  pages  n'ont  pas  ete  filmees. 

Additional  comments  / 
Commentaires  supplementaires: 


L'Institut  a  microfilme  le  meilleur  exemplaire  qu'il  lui  a 
ete  possible  de  se  procurer,  Les  details  de  cet  exem- 
plaire qui  sont  peut-etre  uniques  du  point  de  vue  bibli- 
ographique,  qui  peuvent  modifier  une  image  reproduite, 
ou  qui  peuvent  exiger  une  modification  dans  la  metho- 
de  normale  de  filmage  sont  indiques  ci-dessous. 

Coloured  pages  /  Pages  de  couleur 


Pages  damaged  /  Pages  endommagees 


(      I    Pages  restored  and/or  laminated  / 
L I    Pages  restaurees  efy'ou  pelliculees 

□   Pages  discoloured,  stained  or  foxed  / 
Pages  decolorees,  tachetees  ou  piquees 

Pages  detached  /  Pages  detachees 

Showthrough  /  Transparence 

I      V  Quality  of  print  varies  / 

LiJ    Qualite  inegale  de  I'impression 


Includes  supplementary  material  / 
Comprend  du  materiel  supplementaire 

Pages  wholly  or  partially  obscured  by  errata  slips, 
tissues,  etc.,  have  been  refilmed  to  ensure  the  best 
possible  image  /  Les  pages  totalement  ou 
partiellement  obscurcies  par  un  feuillet  d'errata,  une 
pelure,  etc.,  ont  ete  filmees  a  nouveau  de  fa(pon  a 
obtenir  la  meilleure  image  possible. 

Opposing  pages  with  varying  colouration  or 
discolourations  are  filmed  twice  to  ensure  the  best 
possible  image  /  Les  pages  s'opposant  ayant  des 
colot  ilions  variables  ou  des  decolorations  sont 
lilmees  deux  fois  afin  d'obtenir  la  meilleure  image 
possible. 


n 


This  itrm  is  (ilmed  at  Ihc  rrductinn  ratio  rhpclied  below  / 

Co  document  est  tilme  'i;  tjii«  dc  reduction  indique  ci-dessous. 


10x 

14x 

18x 

22x 

26x 

30x 

1 

1 

I 

_j_  J 

12x 


16x 


20x 


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28x 


32x 


The  copy  filmed  here  has  been  reproduced  thanks 
to  the  generosity  of: 

J.J.  Talman  Regional  Collection, 
D.B.  Weldon  Library, 
University  of  Western  Ontario 

The  images  appearing  here  are  the  best  quality 
possible  considering  the  condition  and  legibility 
of  the  original  copy  and  in  keeping  with  the 
filming  contract  specifications. 


Original  copies  in  printed  paper  covers  are  filmed 
beginning  with  the  front  cover  and  ending  on 
the  last  page  with  a  printed  or  illustrated  impres- 
sion, or  the  back  cover  when  appropriate.  All 
other  original  copies  are  filmed  beginning  on  the 
first  page  with  a  printed  or  illustrated  impres- 
sion, and  ending  on  the  last  page  with  a  printed 
or  illustrated  impression. 


The  last  recorded  frame  on  each  microfiche 
shall  contain  the  symbol  — ^  (meaning  "CON- 
TINUED"), or  the  symbol  V  (meaning  "END"), 
whichever  applies. 

Maps,  plates,  charts,  etc  ,  may  be  filmed  at 
different  reduction  ratios.  Those  too  large  to  be 
entirely  included  in  one  exposure  are  filmed 
beginning  in  the  upper  left  hand  corner,  left  to 
right  and  top  to  bottom    as  many  frames  as 
required.  The  following  diagrams  illustrate  the 
method: 


L'exemplaire  film^  fut  reproduit  grace  i  la 
gdn^rositd  de: 

J.J.    Talman  Regional    Collection, 
D.B.   Weldon   Library, 
University  of  Western  Ontario 

Las  images  suivantes  ont  dt6  reproduites  avec  le 
plus  grand  soin,  compte  tenu  de  la  condition  et 
de  la  nenet*  de  l'exemplaire  film*,  et  en 
conformit*  avec  les  conditions  du  contrat  de 
filmage. 

Les  exemplaires  originaux  dont  la  couverture  en 
papier  est  imprim4e  S(       film6s  en  commencant 
par  In  premier  plat  et  en  terminant  soit  par  la 
derniire  page  qui  comporte  une  empreinte 
d'impression  ou  d'illustration,  soit  par  le  second 
plat,  salon  le  cas.  Tous  les  autres  exemplaires 
originaux  sont  filmAs  en  commenpant  par  la 
premiere  page  qui  comporte  une  empreinte 
d'impression  ou  d'illustration  et  en  terminant  par 
la  derniire  page  qui  comporte  une  telle 
empreinte. 

Un  des  symboles  suivants  apparaitra  sur  la 
derniire  image  de  cheque  microfiche,  selon  le 
cas:  le  symbole  — ♦-  signifie  "A  SUIVRE".  le 
symbole  V  signifie   "FIN". 

Les  carles,  planches,  tableaux,  etc..  peuvent  etre 
film^s  i  des  taux  de  reduction  diff6rents. 
Lorsque  le  document  est  trop  grand  pour  etre 
reproduit  en  un  seul  cliche,  il  est  film*  d  partir 
de  Tangle  supirieur  gauche,  de  gauche  ^  droite. 
et  de  haut  en  bas.  en  prenant  le  nombre 
d'images  nAcessaire.  Les  diagrammes  suivants 
illustrent  la  mdthode. 


1 

2 

3 

1 

2 

3 

4 

5 

6 

MICROCOPY    RESOtUIION    TEST    CH4RI 

ANSI  u..d  ISO  TEST  CHART  N>      ; 


1.0 


I.I 


mil  i.8 


1.25 


'•4     111.6 


^      -APPLIED  \f\MC^ 


f     t 


On  the  Toxicity  of  Various  Commercial 
Preparations  of  Emetin  Hydrochlorid 


iv     I.     1. 1'  \  ^■,    Ml). 

AMI 

I.    I ..    i\  <  >  w  \  T  k  r  I..    M.I). 

i'.  M  ri  Ml  ii<i- 


h'rfiiiiird    iiom    the    .h.hirrs    ,>f    hilcniol    Mcluinc 


Aviiilc  «v    MimcAl.  As-niUTinv 

lui     llrM,,!,,    ,,,n  Thiiitv  livp    NcinTii    IlrMiFniiv    Smre 

19lfi 


ox      nil.      TOXICnv     OF     \AR10US     COMMERCIAL 

I'K'I-.I'ARATIOXS     OF     FMKTIX 

HVDROCHLORID* 


R.    I,.    IVXY.    Mn. 


ANn     I..     (;, 
nAi.riMORE 


ROWKTRFF.     M.n 


In  VK'w  „i  thr  wido^.irca,!  n^c  of  oiiictin  hydrodilnrid  in  the  treat- 
"iint  ,,1  anid.i.  .h^cntrry  and  of  pyorrlica  alvi'olaris,  more  precise 
knowledge  .,1  tlie  toxicity  of  the  coiuniercial  preparations  emjiloved  i. 
higlily  desirable.  The  following  case  reports  forcibly  emphasize  this 
tact: 

Case    F-I.    R     (Me.l.    Xo.    ,1^209).    wliito,    n,alo,    aso.l    %     a    native    of 
Balmnore    wa^   a-lnnUc.l  to  ,l,e  surgical   service  Oct.  u'vm.  co^p  ^n  ^  o 
an     uFcat.-u  r.ctutn."    I-,ttcen  y.-ars  previously  lie  !,a,I  !,a,i  a  cha.u-re   follow^, 
by  a   secon<ary  eruption.     For  ,l,c  pas,   si.x  years   ,l,ore  ha  1  be  n  alter  n   ne 
peruKls  of  d,arrl,ea  and  constipat.on.  wi,l,  l,l„o,l  i„  ,|,e  stools  at  times  ^ 

heartTr'TT""  ''"'"^"'T"'  "'^^'^  -^^  '""""'1  ^'ig'"  en!ar«ement  of  the 
I  art  to  the  Uf,.  a  sof,  systohc  murmur  at  the  ape.x  and  some  unpairment  of 
the  p,TCuss>on  note  over  the  maiuihriun..  The  svstolic  pressure  vsas  ISO  nun 
Hg;  d,a.stohc  7(1  The  urine  was  negative.  The  hlood  shoved  red  hood 
curpusces,  ../.>,VRH1;  white  blood  corpuscles,  7,350;  hemoglobin  (Sahli)  92  per 
-nt.  I  h.  .htterentia!  count  was  norn.al.  The  Wasser.nann  react.un  was 
o  unc.     .\ctnely  motile  amehas  were   found  m  the  stooi.  an,l  October  2u  the 

a;:r  :^,:t"''  " """  '"^""'  ^'"^^^ '-''  ^ '-''-'-  °^ '--  -^ 

At  this  time  the  stools  containe.l  a  few  pus  cells  and  a  little  nuicus  but 
repeated  examinations  revealed  no  amebas,  Sigmoidoseopic  .xamination  showed 
no  ulceration  or  blecduig  points;  10  cm.  from  the  anus  there  were  two  smal 
;cars.  probably  of  healed  .ros,ons.  There  was  a  coUM.Ierable  number  of  small 
internal  hemorrhoids.  sni.ui 

During   the   first   three   weeks   of   his   stay   in   the   hospital   the  patient   was 
iiaving  only  one  or  two  stools  -laily.    r'n-ember  S.  however  .liarrheaev  loped 
'...  the  bueenlb  he  had  eh. e„  bowel  movements.     Xo  amel>as  were  foumi  ' 

Inutmct   and   Ceur^c.-Noveniber    17,   subcutaneous    injections   of   emetin 
hsdrcJlor.d    were    begun.      Tliree   times    a    day.    from    the   seventeemh    t o   ,   e 
weny-l,„h,  mclus.ve.  the  patient   received   'L.  grain;  on  the  twentv-    xt?a  d 
.weny-seve,,,b_   ■.   gram ;   and    from    Xovemhor  28   to   December   5.   .^Khts?^ 
./.i?  r      'V"   '"'"   '«-«""""«   the   emctiii    treatment    the   number   of 

stools   lH'""U'   h-~.      Ihe   Mnpr,.vement.   however,   was   onlv   tempo.arv    am     on 
November  26  there  were  nuie,  and  December  3,  eigh-een  stools  in   he  twenty-  ou 
hours.     It  ,s  nou  worthy  tba,    Decnnb.r   10.  !»,.  days  allcr  .1,,.  em,„„   w  fs  ,1 " 
continued,  the  diarrlira  iierm.-.nently  ceased. 

*I-rom  the  .Medical  Clinic  ..|  ibr  \u\m.  Hopkins  ll,,s.,iid 
'Fight  of  tlie  icn  original  tracings  accompanying  this'  article  were  lost 
by  the  engravers  the  records  appearing  in  Figures  1.  J.  .1  4  5  .,„^  q  .,_... 
been  suppbe.l  by  ,he  authors  in  this  .  mergency.  Thev  do  no!  niusiralc  the 
various  points  brought  out  in  the  paper  as  satisfaclorilv  as  di,l  the  oriijinils 
inasmuch  as  they  represent  tracings  which  had  prcviouslv  been  discarded       ' 


I  )(C(MilH'r  4.  a  irarc  of  aliiiiiiiin  .iml  a  Irw  uraniiUir  ra-i^  n|iprari'il  in  tlio 
uriiu  .     I  la^trir  aii.i1.\-i^  sliouiil  ^liylit  siiliac'iilil> 

IJecomlier  8,  tlie  phthalcin  cxcretinii  was  IX  ]irr  cent,  in  Iwo  hours.  Twn 
ilay.s  later,  the  nnnpnitein  nitrii).:en  nf  the  I)1iiiiil  \va~  \\2  niu.  I'l  r  lIKI  c  e.  ;  thr 
urea  nitrogen,  ''_'  mj  ^ill.inlx'  list'  n\raKi|  ilu-  r\i^linre  ni  a  liieh  ijr.iile 
acidosis. 

The  anioitnt  of  all'iniun  hi  ihe  urnie  gradually  increased,  and  December  11. 
(lour  days  hctore  <leath  i  lilooil  appcirrd.  Tlie  pali<nt  ua^  now  sliglul> 
dyspneic  and  ciiinplanu'd  oi  n.uisea  and  pain  ni  ilu-  unihilical  region,  i  )ii  the 
foiirti'cnth,  the  pid-e  was  weak  and  rapid,  tlic  hreathing  was  of  the  Chcyno- 
.siokrs  \,iriet\  and  co.ir-;  talcs  u ,  re  heard  throughout  the  chest,  Mu  li  nk"- 
cMis  had  ri-iii  to  14,oO(l.  Ihe  s\,t,,li.-  Idi">d  ]ir('ssnri'.  whicli  hcfon  had  r.uiL;i  d 
from  ISO  to  lyo  mm.  Hg,  had  fallen  to  95. 

l)(ceinher  1,^.  alter  a  periled  of  niaikeil  dvspnea.  the  patient  coll.ipsid  and 
died. 

The  lipase  content  <if  the  Id 1  olii.ijiud  at   necropsy  was  1,4  ]ht  cent. 


M.CKoI'sV     KIl'Mlir    (UK,     II,      .N.     ?TKVFVSoN) 

/tual:>ii!iLiil  Ijhi'luosis. — S>phi1ilic  aortitis;  chronic  aortic  emlocirdiiis ;  dila- 
tation of  the  heart;  chrotuc  p.is-ive  coiigestioi:  of  the  \iscera;  arteriosclerosis; 
chronic  indurative  colitis;  lnal' d  tuberculosis  of  ilie  lung  .nid  hilic  glands; 
hroncliopiieumonia. 

.Ibslract  of  Xolcs.—Liiii<i.\-:  DitVu-e  hronclioiinennionia.  /.i;\r:  l.oliulation 
distinct;  irregular  patches  of  congestion;  no  focal  areas  of  necrosis.  Micro- 
scopically, the  lolnilation  is  well  defined;  the  cells  in  the  periportal  i-oncs  are 
large  and  granular.  Cells  in  central  portion  of  lohulcs  arc  atrophic  and  widely 
separated  hy  congested  capillaries.  Spl.-i'ii:  Xol  eidarged ;  sliows  congestion, 
Kiiiiu'xx:  W'eiglu.  l.il)  gni.  each,  t'ortex  ahout  .s  nun.  in  thickness.  Striations 
somewhat  irregular  and  slightly  disinrted,  <  llonieruli  indistinctly  seen  as  minute, 
reddish,  translucent  dots  of  ineuul.ir  inteiisiiy.  I'vr.imids  show  slight  con- 
gestion. Pyramidal  striations  arc  regular.  Pelvis  of  each  kidney  shows  some 
ecchvmoses.  Microscopically,  the  .ni'  rirs  show  slight  iminial  thickining.  There 
are  a  few  ill-detined  areas  in  the  ioru\  where  there  is  slight  increase  in  inter- 
stiti.i!  tissue,  and  a  few  areas  of  round  cell  ini'dtr.ition,  llnoiiinuin:  Lymphoid 
eleiiunis  slightly  hyperplastic,  Xo  idceratiou.  11,-uin:  .<light  Hushing  of 
mucos.i  ill  its  lower  portion.  Aiir./c  liilrsliiu-:  The  Innieu  i-  of  ilie  usual  cir- 
rumfereiice.  The  mucosa  is  everywhere  uniform  in  appearance,  tlieic  heing  no 
erosions  or  ulcerations.  It  is  of  a  uniformly  pale  gray,  almost  white,  color,  and 
the  folds  of  the  niueosa  are  indistinct.  The  mucosa  gi.es  ih,  impn  ssi,  ,ii  fr..ni 
its  consistence  of  heing  thicker  than  normal.  The  inueons  nienihriuie  oi  ihi 
rectum  is  slightly  flushed,  and  microscopically  sh.nv-  ni.irkid  iiiidir;ition  liy 
coni-cclive  tissue  ;uid  rouinl  cc  IK 

SuMMAKN--  A  111.111  weiuliiiiL;  1.^.1  i"iiiiuls  (()'», ,^  ko.)  rocei\eil. 
i!;iilv,  siilHiitinudits  iiiiccliniis  ni  einetin  livilnicliluriil  nwv  :i  iieriiiil  of 
twcitlv  days,  Ilu  cr.ioe  diiilv  close  v\,ts  !i^  nfiiiiis  i  <>()  iiie;.i,-  or 
1.,^  nig.  per  ki;  hi  l>il,>.  In  re.cne.l  2"  ur;iii,s  i  1  74  i^m  i.  or  2.=^  iiiR, 
per  kc;. 

.\  iireviotisK  cNisliiij,'  ili.irrlK;i  \\.is  at  first  ;ipp:treiillv  sniiic\vli;it 
imic'liorated.  tluii  iii;irl.e<lK   inieiisiiieil      <  iii  ilie  -iMtciilh  (i;i_\-  of  Inat 


1.  .Sellards.  .\.  \V.:   null.  J-liiis   ll.q.kins   l|o-p.,   l')14.  xxv.   Idl. 

2.  Tliroughout  this  paper  1  grain  is  regarded  as  the  equivalent  of  (i^  milli- 
grams, inasmuch  as  the  dosage  of  the  commercial  preparations  is  calculated  on 
this   hasis. 


iiK'iit  the  ii.itieiit  ciiiiij)l,iiiK(l  of  nan^ca  ami  alKlnniinal  |]aiii.  Albumin- 
uria and  ivliiulruria  a|j|icarf(l  and  fjradually  ini-rrased.  I-"inallv  there 
was  e\iden(e  of  acute  renal  insuriiciencv.  with  blood  in  the  urine  and 
diminution  in  the  '|ihllialcin  oul|iut,  aloni;  with  an  increase  in  the  non- 
lirotcin  nitrogen  of  the  blood,  'riiere  wa-  marked  ai'ido-i^.  as  evidenced 
by  the  positive  SellarcN  tc-i,  r.rDncboiinruinunia  and  \asomotor 
collai)sc  terminated  the  iHcture 

(ASK  2.— A.  (i.  1'..  (  .Mi',1.  X.i.  .i.iSlS),  a  uliili'  Woman,  a^i-cl  .il.  was  admitteil 
lo  tlu-  medical  service.  Marcli  4.  I'M,;,  i-,,m|)Iainiiis  of  attacks  of  ihtvous  sick 
hcadaclu'.  Tlicsc  attack^,  wliicli  >lir  liad  liad  since  cbildliood.  presented  all  tlic 
essential  features  of  mii;raiiie.  I'lKiiknlatidn  nf  tlic  arms  after  exposure  to  the 
sun.  and  occasional  attacks  of  diarrlua  fidlouinir  in.iiscreti<.ins  in  diet,  had  sug- 
gested to  her  physician  the  possihiljiy  of  iirllaura.  I.nt  id  evidence  was  found 
in  support  of  this  diagno.^is. 

Exiimiiialion.—ihi  e.xaminalion.  she  wa-  -nn  to  he  a  thin,  pale  woman  with 
well-marked  pyorrhea  alveolaris  and  uinKivitis.  The  hlooi.  showed  a  profound 
secondary  anemia.  Kepcateil  examinations  of  tiie  stools  revealed  no  ova  or 
parasites,  even  after  the  administration  of  VL-rmifue'es.  The  gastric  analysis 
was  normal.  .\  faini  trace  of  alhmnin  ncjted  in  tlie  urine  on  the  I'irst  examination 
soon  disap])eare(l.     Xo  casts  were  o1>serveil. 

'Ircalnicnt  nil  J  Coins,-.-  .\{  the  suggestion  of  the  dental  department.  U'  grain 
of  emetin  hydrochloric!  was  administered  subcutaneously  each  day  for  four 
ilays.  beginning  April  2.  .Npril  .i  tlie  patient  had  a  slight  chill,  followed  by  an 
elevation  of  tem|)eratnrc  to  101.  April  4  a  distressing  diarrhea  began;  there 
were  ten  bowel  movements  during  the  night.  She  complained  of  aching  all 
over,  (if  pain  in  the  back  and  abdomen,  and  of  tenesmus.  The  stools  at  this 
time  coiuained  large  nmnbers  of  leukocytes  and  a  few  red  blood  cell;..  N'o 
amcbas  were  found.  The  leukocytes  rose  to  13,800.  During  the  following  six 
days  there  were  from  li\c  ifi  ten  stools  in  the  twenty-four  hours,  all  containing 
pn-  and  blond,  .\jiiil  ''.  alliumin  rcajipeared  in  the  urine.  April  11,  six  days 
aftir  discontinuing  tlie  iiiuiin.  the  diarrhea  promptly  stopped,  and  did  not 
recur  during  her  ~tay   in  iln    hns|,ii,d.     The  alhuminuria  also  disappeared. 

Stoid  luhnri-,  pilvic  and  proioseopic  examinations  were  negative.  Following 
the  on.it  of  the  iharrlie.i.  a  toxic  delirious  state  developed,  witli  great  mental 
confusion  and  vi-ual  .and  auditorx  hallucinalii.'ns.  necessitating  the  transfer  of 
the  patient  i.i  ihi  I'hipp-  I'-Ncluatric  I  linic.  In  the  course  of  a  week  the 
|i-ychosis  cband  up.  and  -he  was  discliargeil  mentally  and  physically  nuich 
improved. 

A  htur  frnni  her  lui-hand  rccei\cil  July  l.s  -t.ite-  tli.at  'Mie  is  in  better 
shape  than  she  has  been  for  iwihe  ycar> ;  -he  weighs  11(1'  .  punnds — more  than 
she  has  i\ir  uiigheil  in  bei   life.'' 

.\  siciind  Utiir  wa-  rietixid.  (iriohcr  I.  s.i\in,g  that  s,i\c  fur  an  occasional 
attack  of  migraine,  and  a  fieling  of  weakness  on  exertion,  the  patient  was 
doing   wall. 

Si'.MM.sm  .\m  anemic,  mideniouri-heil  woman,  weighiiifj  95 
|i(innd--  (4,1.2  1%^;.  I.  received  >u!iculaneoit>ly  '^  <,Main  nf  emetin  liydro- 
clilorid  ilaily  for  foitr  d.iys.  .\ii  intense'  diarrhea  developed, 
associated  with  .■ilidniiiinal  p.iin  ainl  tenesmti>.  which  ceased  six  days 
after  di-C(intinui:)L;  the  eiiu'iin  treatment.  .\t  the  same  time  she  was 
in  ;i  toxic  deliriou.s  st.itt,  which  lasieo  tor  one  week.  She  recovered 
rapi(ll\   and  left  the  ho-pil;il  much  improved. 


'i'lie  daily  (lo>c  of  cmclin  was  '-  grain  ( .iO  iiij^.)  or  0.7  w^.  \>cr  kg. 
Two  grains  i  120  nig.)  were  given  in  toto,  or  277  mg.  per  kg. 

The  symptoms  iiere  following  emetin  administration  wer^  quite  out 
of  proportion  to  tb.e  moderate  dosage  employed,  and  the  jiarticular 
preparation  was  sus])erted  of  l.eing  unusually  toxii'.  At  rordinglv,  a 
dog  weighing  10.5  kg.  was  given  10  mg.  suln-ut;;neously  daily  for  three 
day.s.  On  the  third  day  a  bloody  diarrhea  set  in  and  the  animal  died 
on  the  same  day.  .\t  necropsy,  an  e.Mensive  hemorrhagic  gastro- 
enteritis was  found.  This  dog  received  daily  1.0  mg.  per  kg.,  or,  in 
toto,  3  mg.  per  kg.  -appnjxin.ately  the  same  relative  dosage  as  had  been 
given  to  the  i>atient.  Il  will  be  seen  from  the  experimental  observa- 
tions which  follow  that  this  |]articular  preparation  of  emetin  was 
decidedlv  more  toxic  than  usual 


i:x:>i;h!i.Mi,MS    (i.\    .\xi.\i.\i.s 

Studies  were  made  on  sixty-two  .-iiiinials.  the  serii's  conipri-ing 
dogs,  eats  and  rabbits.  I'ive  commercial  preparations  of  emetin  liydro- 
chlorid  were  investigated:  llurroughs  Wellcome  &  Co.,  (  ami)Oules')  ; 
ICli  Lilly  &  Co.,  lam|ioules);  .Merck  iV  Co.,  (crystals);  I'arke,  Davis 
&  Co.,  (ampoules),  and  Sharp  ^:  Dohme,  (hypodermic  tablets). 

Injections  were  made  in  part  subcutancously,  in  jtart  intravenously. 
'I'he  points  particularly  observed  were:  (1)  toxicity;  (2)  elTects  on 
tile  circulation  and  respiration;  (,^)  pathological  changes;  (4)  effect 
on  the  coagulation  of  the  blood;  (5)  effect  on  renal  function  and  the 
development  of  acidosis. 

1.  Toxicity.  A  Siihiiilaiu-iius  Iiij,\ti,iiis.-~-{^ijc  'Yd\>\c  I).  Dogs 
receiving  single  small  injections  of  10  mg.  (  1  to  2  mg.  per  kg.)  show- 
no  appreciable  reaction.  Rejieatcd  daily  injections  of  10  mg.  cause 
death  (usually  witii  gastro-enteritis )  in  from  three  to  lifteen  days 
(average,  seven  to  ten  d:iys).  I'.ither  tliere  is  an  actual  cumulative 
action  of  the  drug  or  an  altered  tissue  response  on  the  part  of  the 
animals. 

Larger  ^ingle  subcutaneous  injections  of  ,iO  to  45  mg.  (3  to  5  mg. 
per  kg.)  cause  death  in  from  two  to  tive  days.  The  same  gastro- 
intestinal lesions  :iri'  found  at  nccropsv. 

Cats  tolerate  larger  dose-.  D,iily  injections  of  from  2  to  5  mg.  j)er 
kg.  kill  the  animals  in  from  seven  to  eleven  d.iys  .\s  a  rule,  the 
anatomical  lesions  present  are  exceedingly  slight.  The  results  in  kittens 
arc  essentially  simil.ir  to  those  in  adult  cats. 

In  rabbits,  daily  doses  ot  5  mg.  (3  to  4  mg.  per  kg.)  are  unifon  Iv 
fatal  in  from  (i\e  to  six  il.iys.  .\s  in  c;its,  necropsy  usu;illy  reveals  but 
slight  an:ilomical  changes. 


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1 'illirnu't'-  111  llic  imu-  iKTc--,ir\  tn  kill  .ivr  ili|iriiilriit  in  mirl  mi 
\ai"iatiiiii-  in  iip\iiii\  n\  llic  iiri'iMiatioii^  n-ci!,  ami  in  part,  |n."iiia]i-,  (jii 
varying;  ilrmTc^  ni  ir--i-laiuc  In  iiilnNu  alimi  ni  iii(li\  iihial  animals. 
\\liair\ir  tin'  '.niM,  tlu'-r  \aiiaiiiiiiN  ,iic  iNtrinir.  In  dugs,  lor 
ni>tanrc.  ,a  lul.il  >iii-aL;r  m  ,i  ni;^.  pir  ki,',  uf  llu  nm^i  tuxii"  ]irr[iar;it'.  ni 
iL^i\c!f  ^ulu-uIaiu'iir,-!\-  killid  witliiii  tlnw  ■la\-,  wliirra^,  1''  nii;.  ]n-v  kg'. 
1)1  aiiuilur  .  I  iinnirfiiai  pri.  |i,;i;iti(pn  i\i|nit\il  cK-Mii  il:i\-.  In  rat-,  14 
nijj;,  ]n'i'  i^^^  ilnt.al  ild-ai^r  i  iif  iPiic  ]irr|i;irali(in  ('au-rd  ikatli  in  three 
'la\-.  w  k.i'ri',1-.  J'l  iiil;,  per  k^;-  ni  .aiKptlu-r  killfij  unK  .al'lri'  M'\cn  davs. 
l-'iir  ininifdi.itv  death  l"i plk p\\  iiii;"  inlra\a'ni pn>  ailniini-,r,itiijn,  t  int;.  jior 
ki;,  in  OIK'  iii^lanoo,  and  IS  hil;.  per  kt;.  in  annther,  were  iicces^arv. 

I  he  >Miiplipin-.  ppI  iiilci\iealiiin  ,i-  a  rnk'  ni,iml'e-t  tlieinselves  two  or 
.liree  d,i\^  Ipelnre  de.ilh  There  i^  ixtreine  imi-enlar  weaknes-  and 
I)roiloniKeil  U  lli.iii,;\  ,  I  lie  aniniaU  lie  mi  their  -ide--  in  the  e,nv^.^  ;|,](J 
;irc  roii--iMl  w  nh  pJilVieulty  Mdre  than  half  pif  the  pI  -^  .hipI  eat-  \(iniit  ; 
iiiaii}   have  iniiiieiiiu-  thin,  tin  I'm  iiupI  -tmil-      Sumi'  ipf  the  dtp--  -iitle.' 

ironi.,  hi 1\   ili.irrhe.i  :  ,i  lew  have  l.iri,;e  iieninrrhaye-  frppni  llu'  Imwcl 

un  the  da\  oi'  death.     .Mu^eiilar  treiiMr-  ue.  ur  oeea-ioiially  in  dogs  aiii' 
raliliils.     Urooliiiy  Iroin  tlie  iiKPiith  i-  unminn,  e~]peeia11y  in  e.'its. 

11.  Iiilnimioiis  Injections. —  (See  lahle  2i.  llu  Ktlial  <iiiglc 
iiitraveii"ii>  d()<e  i~  v ;iri;ilile  (4  to  IS  iiig.  per  kg.  in  dogs,  d  to  lo  mg. 
per  k;;.  in  pal-i  .nul  i>  l.irgelv  plepeiuleiit  on  atliotint,  dilution  and 
ra]iidily  ni  iiiieetupii  In  e.Nceiitional  instances,  dug-  may  temporarily 
survive  -ingle  injeelioii>  of  from  .?.5  ;o  1^  nig.  per  kg.  lull  death 
gcner,ill\  ipienr<  within  two  da\>. 

X'edder'  has  fotiiiil  tli.it  "2r  nig  pir  kg  iiitravenou?l\  i-  the 
ininimtim  fat.al  (lose  iipi-  r.ihhii-,  while  mih-  r.ilihil  plied  as  the  re-iilt  of 
J()  mg.  pel  kg  aplmiiii-tered  -iiheni.niep m-h  .  I  he  rahhit-  tn  wliieh  tiie 
drug  wa--  given  intravencm-lv  iIupI  m  i  irw  -eepnipl-.  .ipp.ireutlv  ,is  the 
result  of  centric  ]iaralysi-.  10  mg,  per  kg,  -iiheiitanei)iisl\  on  two  suc- 
cessive days  is  a  nnil"orml\   fat.il  dose  for  white  rats." 

2.  Effects  Oh  III,-  (iicuhitioH  ,ittd  Rrsl^imtion. — Kvmograpliic 
leeorcls  were  made  w  illi  the  animals  uinier  etiier  ;mcsthcsia  ,ind  electro- 
cardiograms were  taken  on  chloretoned  dogs. 

The  >iilicutaiieoiis  injection  ni  .a  relatively  Large  dose  (4(J  mg.)  in 
.1  dipg  weighing  10.2  kg.  e.iiiseil  mi  ,ippreciahle  fall  in  lilood  jiressurc 
within  fifteen  minutes;  ai  the  eml  of  h.ill  an  liinn  the  pressure  had 
droppcil  iiPiii!  l.-'i  nun  In  l(i<i  nun  I  Ig  (Sec  Fig.  1).  This  was 
])roliahl\  line  III  pail  to  the  iiilliieiM  ,  fii  ihe  anesthetic.  There  was  no 
change  in  the  animal's  Ke!>er,d  KPiidiinpii  Single  sm.dler  Mihcutaneous 
doses  of  10  mg    I  1  111  2  mg   per  kg  i  have  no  i)erce|)iilp|e  elfects. 


3.  Vedtler.  K.  B.-  Jour.  .\iii    Mc.l    .\smi  ,  lOM,  Ixii,  .Sni. 


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III   ^louly  |.uiMMU,l  .n,iiii,,I.,  ^uhurN  (,|   uiaMud  -mall  dailv  -u!,- 

au;nuuu.   injtvl.nn-    ,  1    tn  _'  „,.    ,,,,-  k^,,  ,,  (Iktc  i>  a  nurke.l  'lail  in 

Iiiv.-,-urL'  renin, Imt  uilli  ilu-  a|i|aaraiu-c  of  tuxi.-  ,-vniptcmiv      lii  uuv 

ainnial  ,.i  5,5  !<-.  wliidi  nvruo!  -rvrn  JaiK  injoiions  of  10  iiit,'.  cadi 

tlictv  ua-  a  .lilhrnuv  ,,i  K^i  „ini.  luiuccii  th.  oricnnal  nifasureincnt 

■""'  '''•"  '•''^'"  ""  tli>    '!■'>   "I   ■Ic'atli       Tin.  ,,„].,■  in  tlir  sick  animal,  i, 
rapid  and  Miiall 

llir  I'lfcci  ni  nilrax.nnn-  mjcrtums  depends  ,,n  several  factors- 
111  the  ,|ua^tlI^  mjolcd.  iJi  it>  dilution;  (3)  ihr  rate  ,,r  injection. 
and  n.  a  lessor  extent  ,  4  i  liie  preparation  cmploved  ;  and  i  5  I  the  indi- 
\idiial  -u-ceptih:liiv  of  ihc  animal. 

Tiic  lii-M  .1  ihe-e  1-  ,.l,\i,,ilv  Relatively  Miiali  ani.-nnl-  ,  S  n,  4  ni- 
per  k.c.  I    i;uen   in   Miiall    \ulume    (5   to    10  c.c. )   an.!   rapidh    injected 

cause  an  ahnipt  tail  in  hi 1  pre-^ure  and  death  in  a  few  minute,   heart 

and  re-pnatH.n.  -n.ppni-  -viKh,nn.,udy  (  Fi^s  J  and  ,^  )  Ihe 
lethal  effect  is  due  niamlx  lu  the  loxir  action  of  the  druu  on  the  heart 
»ui-.  le  prnper.  cauM,,.,.  an  a,uie  cardiac  dilata!,,,,,  \\  hdhcr  there  is 
at  the  same  time  a  va-omotor  paralois  is  not  dear.  The  venous 
conscst.on  of  the  ahdmninal  orijan^  snK5^est>  thai  ,hi.  element  nnv 
i'ia\  a  rule. 

On  the  other  lund,  uhen  ihc  eilietin  iv  udl  ddulcd  .an. I  dnnlx 
a.lnnniMcn  d.  -nnicnd,.,,-  do.e,  mav  he  udl  i,on,e,  (  )ne  dot;  n-eidm.;' 
in  ku'  r.,.ucd  1-L'  in^  ,n  200  c.c.  of  salt  sohitim,  dnrimr  a  thirlv'^ 
"•"Uite  penod.  !)c,„I,  fullovved  n  fmal  rapid  cncemr.,...!  injection 
(40  m-  m  10  cc  c  Ihi.  .anim.d  received  in  all  1X.S2  m^,  per  k-,-an 
mm-u.illy  Iar;,'e  .iiihaini 

I  ke  \ariou-  ■  a.mmercial  preparations,  as  udl  a-  diliVrent  Ids  from 
th.  -.me  iMin.  \ar\  sMineuhat  in  toxicitv  (  Tahles  1  and  2.  and  Ca-e  'l 
Haermai.n  and  iienuniaiin'  have  made  a  -imiiar  ol.ser'vafion  ]t"is 
<l.flKult  to  .^auKc  accurately  the  extent  of  this  variation,  since  animals 
I.Ue  human  hem,-.  .app.nentU  -1,,,^  ditVerences  in  their  in.lividn.d 
tolenmce  tor  the  dru'..; 

l'olIouin«  the  intravenous  injection  of  a  non-lethal  .lose  there  is  a 
pi"inpt  tall  nt  hl,„,d  pressure  of  from  20  to  140  nun  U^  varviuir 
accord.nK  lo  the  con<Iitions  of  the  injection.  The  pressure  rapidiv 
returns  m  ,is  u.rmer  or  even  to  a  higlier  level.  I  here  niav  he  recoverv 
from  alarmiiiyly  low  pressures  i  |'i,_r  4, 

...,Ly:.,S!rTL''T:;„;,,''k'B,.l.j;..ii.7:'K:'';/;;:,'L:S'v''',v' 

J.Mir.  l'h..rnu.ol,  and  Kxpe,-   The  ap..  191.S   vii    l.^))  Lamson.  P.  D.. 

M«  anTmn"'  '''  """"^  "'•"'^'"■■'""'  "-   Munchen.  ,„ed.  Wchnscl.r..  I0I.5.  Ix, 


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In  M,mr  ,.1  the  anunaU  ;.  r,  n.arkaMc  ranliac  arrl,Ml,;,„a  ,^  ,,l,.crvol 
Iherc  1-  a  ~n,l,!.,n  irauMii..,!  in,„,  t|„.  nnrnial  kMnuyiapliio  tr  ui,,.  „, 
one  show,,,;,  u„k,  ,n,.„i,,  ,,,,,,,.  ,  |,,^^  ,  ^,„;|  ,,,  ^_^  ,i,,„,„^-al! 
.n  Woo.l  i,rc..u,v  and  .l.ath  fr,.,„  aau,-  ,ar,lia>-  ,l,lalat,n„  n,av  t„ll„u 
tins  .m•gula^t^,  or  the-  ,u.,n,al  iraonn.  at  a  I„^^1kt  K^d.mav  1,. 
^•>..„,c,l  ,].,^.  5  an,l  r,,.  l;k..„-,„ard,o«ra|.hK-  .!udu.>  i.avc  .liown 
ll.at  ,ln.  ,nv,ulari,>   w  diu-  t.,  a  coar>.  (>,,.  .„   vau.icular  lil.nllati,,,,  ^ 


tiilic  one  Imia-  prior  t. 


k.iJ.      K.cinul   .'.,-5   will-   .Idoicioiie   l.y    slomacli 


tran.,t,o„  t„  cnars.-  ,>,,<.  „f  vu.tricular  r,l.r,llation.       '  '^""^"•■"' 


?ho\V5 


In  ordrr  tliat  thr  nuvhaniMii  ni   cardiac  dcall,  niidn  la    ul^crvcl 
n.cd,an   tl.oracoton.y   ua.   done   „,   an   ani.nal    ,ovi.i„.   intratracheal 

^emndc-^   The  annclc.  ,l,cn  cca-cd  t„  cn.ract.  hcconiin.c  ensorgcd 

o   n  I   ;■'■'  "^"'"'  "■'^^■"^^■■■^  spontaiuously  „<,r  can  it  be    cftorc     t"  .< 
no nnal   luncon   l,y  any  nictbo,!   i„  general  use   for   the  treat.nent  of     -,    li ' 

climcal  .Kajh  .  Ko,,inson,  <;.  CM  ^  l'^;;^.  '^:;,^i  ',^[  ~'-'v  ^"- 

in  C'eSSes""'  ^'-^Crac^  Aro.Iern  Me.licine.  ic.  106)  siates :  ••Fibrillation 
tru  Mitncle^  .  .  .  ,s  sinnlar  m  tlie  condition  of  fibrillation  in  tbe 
aur,.-c.:  wben  ,t  conu..  coordinate  svMole  in  the  ventricle  is  <u'pende  Z  e 
n  u^cl.  cN  Mh.ts  a  continnous  qnivcrinR  and  ine.Tecive  movcmen  ts  ons  I 
M.elN  death.  In  atnmaU  nnder  experin.ental  conditions  it  i,  of  eNtrendv  com 
Z^-T"!^?'"}  ""■  "'"'■•"'^""'  '-^  iinnndiately  bro„«ht  to  a  staX  11  „  thj 
an  nal.  after  a  few  ga^Puis  resp.rattons  and  tuitchinv  movements  of  asphvxial 
ori«m.   n  mains  perfecllv  Muiescent  "  a  pnv.xiai 

fibrMl"?*"""  »">'"••  '"''-y-  "'■  -'•'*  ''^^  °''^"^'''  "'  •■'  ^^■°'"^'"-  recovery  from 
fihrdlatinn    of   the   ventricles   which   lasted    for   two   second,   at   tl-  e-ulV/nn 

aUa.K  of  parowsnial  tachycardia. 


16 

^'";'  ''''^"-l-.     Ill-  ^■-••■.^1.^...nn,„uM  t„nl,r,l!aic  i,.ra  Inn.. :  imallv 

""':."'^    ';:•"   \;"""'^  "-■  "k-.Ih.x  of  th.  luan  >-onti,uK-,l  in  th^ 

asl„„n,     HLnllan  .,.mrar.i,,„s  ,,,,-siMc.l  tor  hvc  „r  ivn  ,>,inuic.  after 

he  h.ari  iKul  >aa.ol  Lcatint,.      h,  several  inMan.v..  ..p.ciallv  in  cat- 

1.C  heart  01  the  animal.  st,„l,e,l  i,„„u  .Iku.Iv  after  .kalh,  onuinite.l  to 

.ibr.llato  tor  as  lo„..  as  uiu.-u  uuuuw^.     In  a   „„  .  ,|,e  left  ventriele 

was  .onnd  nrn,l^   w.ntraele.i  n,  .yM.le.  the  r„ht  llaMn  an,!  dilated 

i  HTe  ,s  „o  s,j.,„,-K,.,„i  ,.l,.,„^r,.  i„  resimatiun  i  j--,^,.  2  and  fn  unf' 
Jt^t  he.orc  death.  The,,  ,he,-e  a,-e  a^phyxial  ,a.,,.  a,  l„n,  intervals: 
Art.t.cal  ,-e.,,„-al,nn  ,.  nnavailino  i„  ,,.„,,„„.  „„  ,,,,,,j  „,,,,,,  ,,„^.^.  j^ 
I'as  ceased  ,„  I,,,,,  CnalK  lua,--  and  n-.pnat,,,,,  M,.p  ,„-ae,iealK 
.-y„ehi-oi,(,iisl_v  I  I'l-,.  2  and  S,,  \     i  <>. 

(  nt.in.i.  the  va,i,d  hefo.v  or  after  the  in,eei,on  prudneed  „n  elVeet  in 
the  response  {  l-\g  S). 

_      .V   J'athohgio.l  iluuuys.-     In  ,/.„,..   ,he  eharaeter.stic  legion   i.  an 
.nflan„„a„on   ,.,    the    .aM.a.inteMinal    trac.      The    .arhe^l    change    is 
ohM-rved  ,n  an  animal  aeuteh    poisoned  hy  intvaven„n.   utjeetio,"  and 
^l>.n|;  at  tl,e  e,al  ,„  ahunt  an  hour.     There  is  „dl  delnied  n.ieetion  and 
Mvelhn;,  o,   the  ,nn,„n~  men,h,-ane  of  the  nnall  ,ntes,ine,  e;poeiallv  of 
l.e,le„,n.     \\l.e".lea,l,,,e,n,-..uhi,,a,V.   nnnn,...,hehea,-tisf,;,,,d 
"^"•;-"''""-  y  '•''•■'•"l.  1"  'I'.-.MohV  Mand-till.     \\  he,-e  entailer  ,|„antitie> 
are  .njected   ,„t,■a^en„n.lv.  „r  da.lv   M,h,  ntaue,  „■..  niiectton.  are  ..iven 
over  a  bn.^er  penod.  and  the  annnal  M.r^ue.  „.r  tuentv-fonr  hours  or 
>'''"e.  there  ,.  a  m  ve,e  ,a^tr„  entern ,.  ,„ten  hemorrhagic  in  character 
Ihe    „,i,cous    memhrane    nf    the    nncMnu-    i,    .pollen,    its    ve^-eN    a,a 
o..j;or^ed  and  a  n,nc„p,„  „Ie,n   exudate  n,,,v  >,.,,•  ,,„nion,  of  its  H,r- 
''",/"'"'""""-  '"■''^""--"■—-cnnnnn      The  dettm  appears 
'-"'•-•»'-'■  .^>>ho.,,h  the  en,,,v  ,ast,-,M,,,est,nal  trac.  •.fn,n,!'rdn 
'oa.np.     '-o„,e,„ne.   .died  u„h  a  hloo.lv.  „„,coidn,aterial.      In  two 

tite  (lU(jclenu,ii  an.l  nj-per  leinnnni 

Microscopicalh,-    there    ,..    n,a,ked    e„n,e.„„n    and    edcna    of   the 

n.uo.a:   -uhn,ucosa   and   ,nuMularis   p.-esetn   .ntdar   hn,    le--   ,narke,l 

lun   ev      1  he  adjacent  n.e.enleric  fat  ,nay  he  cono,,ted  „„;  ,„,„„,.„ 

All  the  ahdo,nn,al  o,-n,an.  a,e  en,.„-,,.ed  ^^\xh  hlood.     The  liver  and 

k.'lne>-.  hot,  srossly  an.l  n„cn,-,.„pi.  alK,  dn.v  con,e-,ion  and  clon,lv 

suelhn^.  ,e.v   -.nall   he,norrha,e.  a,e  -nneti.nes  observed   in   the 

-al  tnednll,,       In  one  ,ns,ance  ,he  en,i,e  head  of  the  pancreas  n-a< 

>urroun,led   and   ,n„hra.ed   1.    .  x„-av,as,ued   Mood,    .huh    under  the 

...K-roscope  was  seen  ,o  Ik.c   forced  Us  .ay  hc.een  the  lohules.     I„ 

us  ~„u„al  .here  .a.  a  snhcap.,lar  he.nor.ha.e  into  the  cortex  of 

tic    k>d,ex._     I.ronchopne.unnn.a    and    pnlmonarv    edema    each    were 

observed  twee  ,„  association  with  the  usual  intestinal  lesions. 

8.  We  arc  i.wiCncI  ,o  n.  T.  V.  S„ru,u  for  note.  o„  d,e  .nicro.copic  pad,oIosv. 


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111  lilts  lutii  rui'hils.  |>athiiluui,-.il  cli.iii-i^  ;ii\  ^li-ht  ami  iiu-(iii-taiit. 
I  Ik'Tc  is  ,s,'(ni.rally  -diiic  iiiirctidii  ni  tin-  m—vU  irf  Uu'  u]i|ai-  ])(irti(in  ni" 
llio  Miiall  iiducl,  rill'  li\tr  an.l  kuliu\>  avc  iuiiov-t>  .1,  and  in  i-ldwiy 
pdiMiiiid  anini,il>  ^\h,:v  >  Icnuly  -wrllini;  in  cnc  cat.  Iiriiiijfiiiar;c 
(Kanirrid  in  iIr-  hcA  nijiiin  ;  in  anuiiirr  iIrtl'  was  a  iiiiM  L;ra(lc  i.f 
I'lilmfiiiary  ccKnia. 

I  lit-  ti  iiilrney  \n\-  rajjliit--  jKii^iMnii  hy  cnutin  (Kia^ionalK  In  (Icvclup 
iiciiiorriia.Liic  |nilnionarv  Ic^Kin-  la-  \<vv\\  \\n\v<\  \>\  a  nnnilHT  nf  |ii<\i(,us 
cili>tT\ors.  i  iiis  lias  lncii  lapiiliinnd  jiy  limlrii;  in  one  (it  nur  animals  a 
jiatcliy,  iu'iiidrrhat;!!-  iirdniiidpncnniunia  with  a.iua!  Mcf.lini,'  intn  the 
liin,<,' tis-iif.     .MirniM-,,],i,-allv.  tluTc  tnnld  hr  -irii  -cxiTal  tmint- df  niii- 

tiiia-  in  the  -nialldr  artt-ru'-  of  ihe  Iuiil;.  ivdiii  whirh  hi I  wa-  pdinain,' 

mtd  tlu'  alvddii. 

4,  liffi-ct  o)i  the  ('.HUjulalio)!  ,<{  llw  lUrod.—\\  wa-  iidt.'d  that  the 
hlddd  of  poisoned  aniiiiaK  cldtted  nnn-nallv  .ld\\l\  and  that  tlie  .ddt  \\a> 
ndiin1ra>-til,-  m  .liara.ler.  S<'vt-ral  -pivnnen-  di  hi,,,,,!  wcit  examined 
hv    l'rdt\...,,r   11,, well,  wh,,  h.a-  \er\    hni,ll\    made  the   l'.  ill, , win-  n.ites: 

D(«;  1.— Utmlit.  10  kv..  Givci-  45  ihr.  emctiii  lydroclilori.l  Mi!,cut;uiedii-1\. 
On  tlic  folIewitiK  (l.iy.  profuse.  lil,)Ofly  diarrlKa  ami  vonutini;.  Dcaili  <.ii  iliin! 
■lay.  I'.lood  for  e\nmiiialion  taken  on  v,coiicl  day:  eoll,c!e.l  in  ,.\,dalc  -oliuiou; 
|'i..<iaa  ycllowisli. 

I  lie  dx.d.iied  plaMiia  with  tlironihiii  soliitioiK  i;a\c  a  clear.  ^nli,I  clot  uliicli 
u:,.  .ntirely  noi.relraclile.  liaxiiiK  the  same  soft,  jelly-like  collsi^le1lcv  that  is 
obtained  m  Mood  to  which  Xa.COj  has  been  ad.led  to  distinct  nlkaliue'reaction. 
riii-i  plasma,  levied  with  neutral  red.  .cave  a  reaction  towanl  the  acid  >ide. 
Under  the  iiltramicroscope,"  the  dot  .bowed  no  visible  striicliirc  whatever, 
whereas,  the  lu.i  mal  clot  show<  a  nia-.s  of  inlerlaciim  necllc-  or  -piculee. 

I).ii;2-1.  Wiiulit.  14  5  kL'  K.eu\,,|  Ml  inK'.  emeiin  Iiy,lrochlonrl  intravenously. 
Die. I   in  thiriy  hours   wiili  a   bemorrli.iHic  i;a>tro-enieriti<. 

.\, specimen  of  bloo.l  was  taken  immediately  after  death.  oN.ilati.I  and  eeiitri- 
fiiKalized.  Plasma  very  scanty  in  amount  (about  half  ii,.nii.ili  ,iiid  vellowish 
in  color.  \\  li,  n  iliriinibin  solutions  were  added,  ch.tiini:  u.,-  sl,,u-  anil  imperfecu 
as  thonuh  t)l.riii,.«,  ii  were  delicieiit  in  .Mii.nini.  Tin  liiial  result  was  a  tlo.itim.' 
clot. 

Lnder   the    ultramicroscope    snnie    librin    necilles    formed    Init   were   scanty 

.'■cattered  needles   or  small  clnmps  of   needles  in   place  of  the  thickly  meshed 
needles  of  n,'rnial  pl.isma. 

.^.  Studies  oj  Rriiil  iiiiictii'ii  and  .  I  riih'sis-  -  <v\er:\]  ddL;-  were 
Used  liir  this  p^u•]lds^^  Alhuniimiri.i  i.e,  nnad  inediistantlv  m  -lnwly 
poisoned  amm.ds.  I'lure  w.a-  mi  appreei.ihle  rediietidii  in  'phthalein 
excretion,  luir  was  tiieix'  an\  niln.i^en  rtlentidii  as  r\  ideiu  ed  hy  the  urea 
content  of  the  Mood,  even  dii  the  ,!ay  preeedini:  de;.lli.  As  a  termin.il 
pl.etiomendn.  en  the  ,l.i\   (if  de.ilh  there  wa-  ndte,!  \erv  sli<,>ht  increase 

''.   In  this  cnnection  see  article  by  I'r.,!,  IP.utll:  Aimr.  Juur    I'hvsiol     1914 
XXXV.   14.1  ■        "        ■■  ■ 


19 

111  the  li\  iliii^cn  inn  tum  cntratiini  of  llic  IiIuimI  -cniiii.  hii'  no  chaniic' 
in  tli:it  of  ihe  wIkiIc  IiIoik!,'"  I  lir  C'(  )_,  trn-:un  ul  ihc  a!\ciilar  air  was 
al-ii  ^onirwliai  IdwiTnl.  in  ijni'  animal  lallini:;  In  ,^,>  mm.  llj^  several 
linur>  Ijvinrc  (iiatli.  Tlii^  ])iiun(imt'niin  has  hcxMi  nottd  Ijv  Mcver  and 
W  iniam>"  in  (.•\]icriinrnlai  cmriin  pui-Diiinu. 


sr.M  MAln 


'I        I'KIAInIS       I.NIl.KIMI.N  lAI.       WORK       oX       I.MllIX 


In  ISl/,  M,iL;rii(ii<-  and  I'lllrtici'-  annninici  d  ill, it  llit-y  liail  iMjlalril  an  i-nirtic 
-ubslauLa-  ('iihiluir  7'umilhr")  irom  the  \>h\ut  fsychotria  cmclica.  1  his  sul). 
stancc  iliey  called  cmctiii.  lliey  loiiiul  tliat  it  had  an  emetic  and  [inrKative 
action  and  tluu  it  po-scsscd  marked  narcotic  |)rn|)crties  when  sivm  to  aninial>. 
In  order  to  determine  the  toxicity  of  the  drne,.  10  j;rain>  were  given  to  a  doR. 
X'oniitinK  and  Mnpor  I'l.lk.ueil,  and  lli.-  animal  died  in  (ii'tcen  lionrs.  "Anatomical 
examination  -liowrd  tliat  the  animal  had  -ncciimhed  to  a  vioK  in  iiillammation 
of  tile  tissue  of  t!.e  Umus  and  of  tlie  mih.ais  niembrane  of  the  intestinal  tract. 
ii"m  cardi.i  to  aims."  After  olitainiim  -imilar  effects  with  a  number  of  animals, 
lbe>  conclndi  d  tliat  "llieve  ol)ser\.iii.'iis  ,ire  important,  inasmuch  as  tin  y  show 
iliat   em  tin,  ,i.;i\rn  in   lar,i{e  du.ses,  may   produce  gravi'   results." 

Diiiiim  the  ruuaiuder  of  the  nineteenth  century,  a  number  of  investigators 
imdertcHik  the  siudy  (pf  iiiecacuaiilia  and  its  uculy  discoverc<l  alkaloid.  Especially 
not,dple  lor  their  comi>leteness  and  accuracy  of  observation  ,ire  the  articles  of 
D\ce  Diickwortli"  and  I'odwyssot/ki."  The  latter  iieited  uiili  wonder  the 
cardiac  arrhythmia  uhicli  we  liave  shown  to  be  uuc  to  ventricular  librillation. 

Of  ftmdamental  importance  w,is  the  work  of  I'anl  and  Cowtdey''  in  l,so,;, 
demoiistratim;  tlial  the  so-called  emetin  ni  previous  workers  w.is  in  rralit\  a 
mixture  of  two  alkaloids— the  one.  eiiulin,  an  amorphous  sulist.ince.  to  which 
they  assiiriied  llie  forniuli  ('  II. .\i)  ;  ilu-  .iihcr.  which  the\  named  cephailiii. 
a  cijsialliii  subsi.uui  lia\inH  ihe  formula  C  ll.\li.  I.niriiu  bvclmclilorith 
Ci.-,H.,Xi  1  lii'l.  i1k\  were  alilc  to  make  in  cryslallin  form.  'I'lie  presence  of  a 
third  alk.ilnid.  psyclminn.  was  determined  by  them  two  \,ais  laid.  il  was 
isnlited  in  small  amounts  as  lemon-yellow,  rliombic  [irisnis  The  ainouiit  ..f 
alkaloids  in  ipecacuanha  they  loanil  to  be  aljont  2  per  cent. 

Willi  '  in  l,s;');,  wiirkiiii.'  for  tlie  iirst  tim.  wiili  iluse  pure  alkaloids,  wliicii 
he  olitained  fr..m  r.inl.  inveslij.;ated  and  iMinpared  their  pharmacolo.aical 
action.  He  fcnind  ih.ii  'h.iIi  emetin  .and  ce|ihaelin  are  emetics,  the  emetic  dose 
of  the  latter  being  h.ilf  thai  of  emetin.  Both  lower  the  Idood  pressure.  The 
deiin-si.iii  prcdncid  In  the  eiiuli.-  d.is,-  .,f  ripharhn  i-  U'ss  ilian  ih.it  pr  .diurd 
I>\  ihe  l.n-Li'-r  fiiutic  dnsr  ,,f  Mueliii.  The  \asciilar  dT'ils  fr.ini  rnirtin  .ire 
gr(ater.     llntli   produce   wiakriiiiig.    T.iwini;  and  ■liasiiilic  .irri  st  of  the  heart. 


10.  Ill   making  ;hcse  deteriuination-.   the  imihoil   recently   described   by   I-cvy, 
Rowiiirec  and  Marriott  was  employed  (  llii    .\k.  iiims  js\.  Mkd.,  1915,  xvi,  389), 

11.  -\Ii\cr  and  Williams:  Arch.  f.  <  \p.  r.   I'.nh,  ii    I'harmakol..  IH8i.  xiii.  70, 
\2.  M.tgendie  ami   i'ellitiir:   lour,  ih-  pli.inn,.   I,s:l7.  iii.   !4,s. 

1,1  Duckworth,  Dyce:  St.  ITiriholomew's  ll,,isp,  Kip.  iSo9.  v.  218;  also  1871, 
vii.  'II. 

14.  I'oilwyssnt/ki :  .\rch.  f.  exper.  P.iih.  u.  1 'h.ii  iiiak.  il..  1.S79.  xi.  2.51. 

15.  Paul.   11.  II..  and  Cownley.  .\.  J.;    riiarin.  .buir.  and  Trans..   1893,  liii.  Ol  ; 
also  1894.  liv.  iii. 

16.  I'aul.  H.  n,.  and  Cownlcy,  A.  J.:  riiarm.  Jour,  au'l  Trans.,  1895.  liv.  6'X). 

17.  Wild,  R.  B.:  Lancet,  London,  1895,  Ixxiii.  1274. 


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22 

Lowiii"  ill  I'HC  ill  a  rixiew  of  privioii-.  wuik  uii  llu-  -ul'in-t.  uivis  a  .nniiili  tc 
l.ibliciKr.iipby  Ui  (lati\  In  addition  to  tlic  facts  ciniilia>i/<  il  I>y  \\  iM,  Ik  iinilinns 
the  cliaractorisUC  ua>tro-intcstinal  Ksion^  fonml  li\  otlui>  in  puisoiud  animals, 
and  states  that  on  tln'  liiiiK^  (im-lin  lia^  in.  ariu.ii.  ulurcas.  in  ccpliaclni  poison- 
in^'.  extravasation  of  blood  into  tbe  hums  was  noted  several  times.  Deleterious 
action  on  the  kidneys  is  found  to  be  more  cliaraeteristie  uf  eephaelin.  Poisoned 
animals  die  of  cardiac  paralysi  ICmetin,  liowevir.  injures  tbe  lieart  in  tinich 
Miialler  doses  tban  <loes  ccphaelin  ;  but  cepbaelin  causes  a  1411  aur  fall  111  bU.ud 
pressure. 

The  mode  of  excretion  of  the  alkaloids  euubl  ii..t  be  .U  tcriiiiiied  by  l.owiii. 
\o  trace  of  then-  was  found  in  gastric  or  intestinal  coiUeuts  or  in  tbe  urine." 
I'inally.  he  determined  that  psycliotrin  need  not  be  considered  in  taking  into 
account  the  action  of  these  alkaloid-;  it  is  presiiit  m  very  Miiall  ain.ium-.  has 
no  emetic  action   and  no  to\ic  action  on   the  bean 

(  Uir  |ihariii.uiil.ii;b-.il  .iii'l  ]  i.itlmld.uu  al  liinlin.i;-  .ire  i|ime  m  aeounl 
Willi  ihii-e  ui  |irc\ii'Li-  iir.e-tii^.itiir-.  while  two  luw  lael-  are  etjll- 
uilmteil  l-'ir-t.  Ii\  ekelnu  .inlinijr.iplih  -tiplu-  il  li;i~  liceii  -liowii  thai 
the  eanli.n-  irremil.iril  \  iii'i-ihuaal  in  eiiietiii  j  .ui-miini;  1-  illie  tn  liiinlla- 
liiiil  (if  llie  ventricle-.  I'niin  wliiili  tiie  .iiiiiii.tU  i!ia\  lei'iivcr  ;  ami.  sceund, 
1 'roles Mil-  lloweir-  i.l.-eT\ali(ins  lia\e  -linwii  .iller.iliuiis  iti  tlie  clottiiif,' 
l)roiK'"'ic's  ui  tile  liliuid 

ILL      lllI.eT.S      lOLLliWINl,       M I  t;      (LINKAL      l>i;      i 'I       1 .  M  I    11  .N 

That  llie  iheiapeulu  .ulinitii-lra.ln  m  ui  eilletiii  shuulil  iml  lie 
rc'sardfil  .1-  .m  alto,i,"-'llHi  iiiniHiuitis  procedure  lias  heeii  ]ire\iously 
iiuled.  II111-.  e\eii  .i-  earl\  ,1-  1S<),^.  Wild'"  ;-a_\  s  :  ■•Hie  lael  ihat  a 
.hhiti.ai  ui  1  in  Jll.iKXi  .aiiMil  diaslolk  arrest  ul  the  l'roK'>  I'e.irt  in 
lorty->ix  niiiiutes.  ri'iiders  eaitlinii  neee--;ir\  in  uivini;  l.ir.oi  r  dose>  ol 
the  alkaloid." 


liaiimami  and  lleiiiemaim'  have  iioled  distre-sin;;  ,iiul  e\en  al.irmiiiK  svnip- 
toms  following  doses  much  larger  than  are  usually  employed.  'I'liey  say:  ".Sub- 
cutaneous injections  produce  in  some  instances  .  .  shglit  general  malaise; 
otherwise,  with  small  and  moderate  sized  iloses  of  (i(l  to  150  mg..  there  arc  no 
symptoms  If  120  to  150  mg.  are  given  in  daily  repeated  injections,  there  appear, 
after  th.cc  or  four  injections,  malaise,  lassitude,  slight  vertigo  and  loss  of 
appetite.  These  symptotns  disappear  in  from  24  to  7Z  hours  after  the  emetin 
has  been  discontinued. 

"Intravenous  injections  of  fX)  to  JlKI  ing.  cause  no  serioii-  ilisliub.iiu  ■■ ;  there 
i,  slight  vertigo,  transient  tlnshing  of  the  face  and  retching.  If  this  dosage 
is  exceeded  and  M».)  to  4(X)  lug.  pre  injected,  serious  symptoms  are  observed. 
These  appear  in  from  two  to  live  mimiles  after  the  injection  and  con-ist  of 
general  vascular  paralysis,  severe  expiratory  dyspnea  with  cessation  of  respira- 
tion, loss  of  consciousness  with  vomiting,  the  passage  of  thin  stools,  and  great 
-lowing  of  the  pulse.    Although  these  phenomena  are  trans. cnt  and  arc  ipnckty 


18,  Lowin,  C. :  .\rch.  iiilernat.  di-  pharmacod.  et  de  therap..  I'>l2.  xi,  'J. 

19.  More  recently,  Lyons  (New  Orleans  Med.  anil  Surg.  Jour..  1")12.  \\\\ . 
KM4l.  using  sterilized  fecal  liltrates  matle  from  the  stools  of  individuals  reciiving 
ipecac  by  mouth,  cnutil  demonstrate  no  amebicidal  properties,  in  vitro,  of  the 
contents  of  the  bowel. 


23 

nlicvcd  li\  Miit;ili1i-  nu'aMir<5.  yil  cm  the  Ikims  of  \hc-,-  ol.s,  rvali.m-  \v.  woiiM 
rcsard  a'^  tlu'  maximal  imravtiious  clo-c  250  mi;.  Tir  ku.  nf  IhhIv  wcmlit.  W  r 
have  never  observed  any  injury  to  the  kidneys,  nor  has  tliere  been  any  per- 
manent  damage   to   the  patient,  even   witli   the   higli   intravenous   doses." 

\eddcr's'  connnents  in  this  connection  ar.  wortli  quoting  in  full.  He  says: 
"Since  emetin.  bv  manv  oliscrvcrs.  has  been  regarded  as  a  more  or  less  harmless 
drug,  and  since  I  am  of  the  opinion  tliat  the  doses  used  by  some,  and  particularly 
by  c'aermann  and  Hcineinann,  are  too  large,  1  wi^li  to  point  out  the  possilde 
danger  in  not  using  due  camion  in  tlie  use  of  thi-  \ir\   pcunt   r<ni..l\. 

"It  would  appc  ar  from  our  experimental  observations  tliat  the  closes  proposed 
by  Uaermann  and  lleinemann  are  far  too  large,  and  that  if  the  drug  is 
adminiMrr.d  in  -n.li  do,e~  'a.al.ti.-  uill  -"'it  occur  wliich  will  uiijn^tly  di-- 
eredil  the  use  c,i  .inuiii.  rnrtlierm..re.  llu■^e  treiuendous  doses  appear  to  be 
entirely  uncalled  i.'i.  si,;e,.  micccss  is  commonly  obtained  in  the  treattnetit  ol 
amebic  dvM-ntcr\  ancl  In  patic  abscess  with  doses  not  exceeding  1  gram 
h\i"idermii'.dl>'. 

"\fter  seeittg  rabbits  die'  innni.haldy  after  intravenous  injections  of  com- 
parativelv  small  amounts  (fr..ni  .i  to  -^  my.  i  of  emetin  hydrochlorid.  /  .r/icU»M 
/i,-5i/.i/,-  lu-fon-  .tdminislcruui  crcn  I  <iiain  inlnuriwusly  in  a  human  case: 
If  given  to  on.  of  the  p.ilients  so  susceptible  to  the  effects  of  ipecac  im-ntioned 
by  Sollmann  '  Mi.h  a  treatment  w..nld  tiot  improbably  be  followed  by  death,' 

I  yons^  from  ehni.al  >  .I.m  rvalion-  warns  against  tlie  use  of  large  doses,  as 
follows:  "Too  large  dose^  cr  t...  pr.donged  u>e  of  tnoderate  closes  may  cause 
a  diarrhea  or  be  responsible  for  its  persistence.  Ilu-r,-  ,.<  vuraisina  cvul.nc- 
lIuU  Uir.ii-  ih'.u-s  of  i-iii.-ln\  ar.-  not  u'itlh'id  ill  c/Jcc'/." '" 


llu-  rcpcrleci  t.i-e.-  m  uliuli  til  elJVet^  lia\c  icdlcwrd  the  >litm-;il  use 
cif  etltetiii  .ire  .t,'i\etl  in  tile  :ii<i  iiii|i.iiiviiii;  lalile   (    Tahle  ■'  >■ 

Tito  exiaTielue  ol  l.v.ni-  witli  tlie  :i.lmiiii~lv:itinii  of  emetin  l.y 
tnoutl'  ineeluiles  it>  iim'  liv  the  oral  icitite  He  I'oiin-l  il  I'XcealiiiKly 
irritant  even  in  sin,, 11  .Icm-  X.niM-a,  \oiiiiiiiil;.  t;rii.itii,',  iniriiation  .an<l 
])crsistent  alMloiiinial  di-eoniforl  tolloucd  llie  inuostioii  of  1  2  '^r.  in 
solnticni. 

lite  case  report.  <1  in  clel.iil  e;irli.T  m  tin-  japer  i-  the  lir-t  in  which 
llie  l.il.ii  n^siilt  ."in  1".-  altrihiitecl  to  tlu  tluTaii.tin.-  ti-e  ot  (iiu-tiii-  <  biiv 
on.'  f.il.ll  e,i-.'  of  iiie.-;i.ti:iiili,i  jx  n-oiiini;  ccnlil  h.'  loiiiicl  in  the 
literature.- • 


2(1.  Italics  ours. 

21,  .Sollmann,  T,:  Text  r,....k  ..t  I'li.inii...  ..1.  p,  ,ill"  1 1  it,  d  bv  \  .■.hi.  r,  i  ".■-..me 
persons  are  so  sensitive  to  the  L.cal  acti.m  of  i|H'Cac  that  the  openmg  ..f  :i  Mr 
at  a  distance  of  several  feet  will  produce  violent   snee/ing  and  cli«comf..rt  " 

22.  l.vons.  K.:  .Am.  Jor-    M.  .1    S.^  ,  l<d.r  el,  'I7 

2.3  llarrison  (Lancet.  I.on.U.n.  VW.  u.  'r^Mn  t.lU  ..t  :i  JO-v.ar  ..Id  .v.. nth  »bo 
"drank  s.x.ral  in.hes  of  a  luiltle  of  vinum  ipecacnaidiae."  One  hour  after 
swallowing  ibi>  d.'se  there  was  uncmtrollablr  vomiting  and  a  rapid  pulse:  the 
extremities  became  cdd  and  -tamp  u.th  perspiration.  Death  occurred  in  an 
liour  aii.l  a  ball.  -\t  necr.ip^s  ih.  le  u...  Imui.l  subacute  couKesti.,,!  ..i  th.^ 
stomach  and  lirM  two  feet  of  the  intestine.  The  heart  was  in  diasiol.-  I  lu 
other  organs  were  normal.  Harrison  comments  that  "the  congeslion  d  the 
stomach  was  .-ertainly  an  insutlicient  cause  of  .leath." 


SL'GCKSTIONS     WITH     Klr.AUH     in    A     HATKlNAI.     IMITIX     TMF.rM'V 

llciw  iiMv  llic  \<<sw  I'lV.H!-  Ill  iiiuliti  lio>l  lie  axdi.kdr  As  the 
result  liuth  of  ■  iioal  aiui  lalioralor)-  olisorvatioiis  tlic  following 
suggestion-  are  iire-enled; 

1.  The  ailiiiini:-tralion  of  eiiklin  li\(lroclilori(l  is  not  to  be  regarded 
as  a  hannles^  inui-edure,  I'.veii  ni  llieraiH'Utir  iloses  ill  effects  may 
follow  its  use. 

.'  lii,livi('iuali/alio!i  l.y  elo-i  rlnii.al  oli-ervalion  i-  e-<ential  both 
for  tin  MU>i--  and  safety  ol  llie  tnaliiieiit.  ratient-  may  differ 
iliaiKedK  ui  tlieir  -u-.-e])tiliilit>  lo  llu  diui;,  and  the  \ariou-  .oinmereial 
preparations    \ary    widelv    m    tosi.  ity  llie-e    poiut>   are    strikingly 

demonstrated  h\   llie  t<i\i>  itv  e\i'erinieiit-  herein  rejiorted. 

,v  idle  ireatnient  dionld  he  given  in  cour-e-.  at  intervals  of  several 
da_\>  or  a  week.  llu-  -ulicutaiieous  route  i~  the  one  of  elioiee.  Indi- 
viilual  dosage  and  the  .luration  of  eaeli  rour-e  inn-t  he  determine<l  hy 
the  exigeneiesof  the  ease.  One-thir<l  grain  tlirre  time-  a  d.iy  lor  .1  week 
or  ten  days  is  usually  a  >afe  dosage  in  amehie  infeetious.  It  is  rarely 
necessary  to  give  more  than  l'^  grains  daily.  In  the  treatment  of 
pyorrhea,  Bass  and  Johns'-^  advocate  'j  grain  d.iilv  for  from  three  to 
six  davs.  and  maintain  that  no  ease  need  have  more  than  -ix  da\ -' 
treatment.     I 'iider  ordinary  eireunistanees  thi'-  -ein  "  witliin  the 

man^in  of  safetx'.     it  mn-t  he  home  in  mind,  howevi  thi   .idinin- 

i-tralion  of  even  ri'lati\el\   -m.ill  do-e-  oxer  a  lont;  p(  ,uid  >  :  Iniie  niav 
prove  liarmful. 

4  I  he  l.irgc  dosage  advoi"'.t>.ii  h>  l'..iernianii  :ind  1  leineinaiin  is 
imiieee-sary  and  dangeroU';. 

5.  Intravenous  injeetions  should  hr  em|iloyi<l  only  ni  extreme 
cases.  If  this  mode  ><\  admini-lralion  -eem-  im|ier.itui',  -mall  doses, 
well  diluted  (  '  :■  Srain  in  101  e  e.  -alt  solution  1  -hould  he  -lowlv  given, 
and  the  hlood  pressure  should  he  e.irefully  observed  rjuriiig  the 
injection. 


24.  Bass.  C.  C,  nnd  Joliii-.  IM      .h"u     \.n    Me.l.  .^^sii..  101.-.  Ixiv.  .=;.i.V 


•      • 


